On August 5, 2021 Exicure, Inc. (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported that it is providing an update on the Phase 1b/2 clinical trial of cavrotolimod (AST-008) (NCT03684785) (Press release, Exicure, AUG 5, 2021, View Source [SID1234585941]). The Phase 2 stage of the trial is evaluating cavrotolimod in combination with pembrolizumab (KEYTRUDA) or cemiplimab (LIBTAYO) in patients with locally advanced or metastatic solid tumors refractory to anti-PD-(L)1 therapy in two primary dose-expansion cohorts, one in MCC and one in cutaneous squamous cell carcinoma (CSCC), and three exploratory cohorts.

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Interim data highlights from the Phase 2 expansion stage

As of the data cut-off date of July 1, 2021, 26 patients, all with documented progression on anti-PD-(L)1 therapy, have been dosed in the Phase 2 stage, of whom 17 patients were evaluable.
Nine of the 17 evaluable patients were in the MCC cohort and, per RECIST v1.1, best overall response was a complete response (CR) in one MCC patient and stable disease in one MCC patient.
Injected and non-injected tumor lesions completely resolved in the MCC patient with a CR, supporting systemic (abscopal) effects.
The CR in one MCC patient met the pre-specified Phase 2 stage threshold to continue advancing patient enrollment in the MCC dose-expansion cohort.
The remaining 8 evaluable patients were enrolled in either the CSCC dose-expansion cohort, in which enrollment and data accrual is continuing, or in the exploratory cohorts.
The majority (93%) of treatment-related adverse events (TRAEs) were grade 1 or grade 2. The most common TRAEs were injection-site reactions and flu-like symptoms.
Two patients experienced serious adverse events assessed as related to cavrotolimod by clinical trial investigators. Treatment-related hypotension and flu-like symptoms were reported in one melanoma patient and a treatment-related injection reaction was reported in one MCC patient.
The confirmed ORR in all evaluable MCC patients enrolled in total in the Phase 1b/2 trial was 21% (three of 14) as of the July 1, 2021 data cutoff date.

The three patients were comprised of two CRs and one partial response (PR).
Biopsy of individual tumor lesions of the MCC patient assessed as PR by RECIST v1.1 revealed no evidence of residual tumor.
As of August 4, 2021, total trial enrollment for the Phase 1b/2 trial including primary and exploratory cohorts was 51 patients.

"Merkel cell carcinoma is an aggressive skin cancer with a high probability of metastasis. Observing a patient with metastatic MCC who had been previously progressing on pembrolizumab monotherapy and radiation, achieve a complete response, is highly encouraging," said Dr. Sunandana Chandra, M.D., Assistant Professor at Northwestern University Feinberg School of Medicine and principal investigator in the Phase 1b/2 clinical trial of cavrotolimod.

Trial results and further response details are summarized in the company’s updated corporate presentation on the Company’s website.

About Cavrotolimod (AST-008)

Cavrotolimod (AST-008) is an SNA consisting of toll-like receptor 9 agonists designed for immuno-oncology applications. Cavrotolimod is in a Phase 1b/2 clinical trial in patients with advanced solid tumors. In December 2019, Exicure announced preliminary results from the Phase 1b stage of the clinical trial including potential signs of anti-tumor activity with cavrotolimod in combination with pembrolizumab in cancer patients. In the second quarter of 2020, Exicure initiated the Phase 2 stage of the clinical trial with dose-expansion cohorts of intratumoral cavrotolimod in combination with approved checkpoint inhibitors to treat two cohorts of patients with locally advanced or metastatic MCC or CSCC. Additional information regarding the Phase 1b/2 study can be found here: View Source Cavrotolimod in combination with anti-PD-1 therapy was granted Fast Track and Orphan Drug designations for locally advanced or metastatic MCC refractory to anti-PD-(L)1 therapy and Fast Track designation for locally advanced or metastatic CSCC refractory to anti-PD-1 therapy.